Description: (Applicant's Description) The Prostate Cancer Program is comprehensive, encompassing basic, translational and clinical research. Four areas which are emphasized are 1) development of new model systems, 2) studies on the progression, recurrence and metastasis of prostate cancer, 3) development of novel therapeutic targets and therapies and 4) racial differences in prostate cancer. One model system, the SCID-hu model is used to study human prostate cancer metastasis to bone, the role of adhesion molecules in homing to the bone environment, the role of metalloproteinases and cathepsins in bone tumor growth and various angiogenic factors that control vascularization of tumors in bone. In the study of tumor progression, precursor lesions (high-grade intraepithelial neoplasia; HGPIN) are being used as markers to study the effects of selenium on formation of prostate cancer. Other studies examine prognostic markers associated with progression of organ confined cancer. The prognostic significance of circulating and bone marrow micrometastasis is also being evaluated. Basic research on apoptosis-related genes, proteinases and lipid and carbohydrate molecules, which may stimulate metastasis and angiogenesis form the basis for development of novel therapeutic targets and therapies. Neutron therapy has been used to enhance the efficacy of radiotherapy in prostate cancer and studies on gene therapy, which target metalloproteinase enzymes are underway. In addition, new chemotherapeutic agents targeting lipid metabolizing enzymes have been discovered as well as inhibitors of a carbohydrate molecule that inhibits apoptosis and stimulates angiogenesis. An underlying theme in these studies is the search for "biologic" factors that may explain the higher tendency for tumor progression in African American males. These studies involve a focus on HGPIN, which is more prevalent in African American males, genetic analysis of hereditary prostate cancer in this group of individuals as well as the influence of diet. Finally, the program has developed an interactive and integrated Multidisciplinary Prostate Cancer Database that has provided researchers easy access to clinical, pathological and diagnostic information on patients whose tissue resources are used in their study cohort. The twenty research members of this program have in excess 4 million dollars (TDC) in peer reviewed grants.